crossing96/oncoscreening huggingface dataset:
Combination of Erlotinib and Naproxen Employing Pulsatile or Intermittent Dosing Profoundly Inhibits Urinary Bladder Cancers.	Daily dosing of either NSAIDs or EGFR inhibitors has been shown to prevent bladder cancer development in a N-butyl-(4-hydroxybutyl)nitrosamine (OH-BBN)-induced rat model. However, these inhibitors cause gastrointestinal ulceration and acneiform rash, respectively, limiting their continuous use in a clinical prevention setting. We studied chemopreventive efficacy of pulsatile dosing of EGFR inhibitor erlotinib (42 mg/kg BW, once/week) combined with intermittent or continuous low doses of the NSAID naproxen (30 mg/kg BW/day, 3 weeks on/off or 128 ppm daily in diet) in the OH-BBN induced rat bladder cancer model. The interventions were started either at 1 or 4 weeks (early intervention) or 3 months (delayed intervention) after the last OH-BBN treatment, by which time the rats had developed microscopic bladder lesions. All combination regimens tested as early versus late intervention led to the reduction of the average bladder tumor weights (54%-82%; P < 0.01 to P < 0.0001), a decrease in tumor multiplicity (65%-85%; P < 0.01 to P < 0.0001), and a decrease in the number of rats with large palpable tumors (>200 mg; 83%-90%; P < 0.01 to P < 0.0001). Levels of signal transduction markers, Ki-67, cyclin D1, IL1β, pSTAT3, and pERK, were significantly (P < 0.05 to P < 0.001) reduced in the treated tumors, demonstrating their potential utility as predictive markers for efficacy. These findings demonstrate that significant chemopreventive efficacy could be achieved with alternative intervention regimens designed to reduce the toxicity of agents, and that starting erlotinib and/or naproxen treatments at the time microscopic tumors were present still conferred the efficacy.	bladder
A high sensitivity background eliminated fluorescence sensing platform for hyaluronidase activity detection based on Si QDs/HA-δ-FeOOH nanoassembly.	Using fluorescent sensors for highly sensitive and selective detection of biomolecules is a very important strategy in clinical diagnoses as well as biomedical applications. But fluorescent sensors usually suffer from high background signal, which greatly hinders their detection sensitivity. In this work, a novel background-eliminated fluorescence assay for sensitive and selective detection of biomolecule has been developed by coupling feroxyhyte nanosheets (δ-FeOOH) with amino-functionalized silicon quantum dot (Si QDs). We select hyaluronidase (HAase) as the modal target to verify the concept. Si QDs/HA-δ-FeOOH nanoassembly was fabricated by self-assembly of positive Si QDs together with negative HA-δ-FeOOH through electrostatic adsorption. By the introduction of hyaluronidase, the nanoassembly exhibits obviously fluorescence signal recovered. Research suggests that under optimized conditions, this strategy exhibits a good linear response to the concentration of HAase in the range of 0.1 to 12 ng/mL. The detection limit for HAase was 0.02 ng/mL (based on 3σ/S), which was three-order lower than most of the reported fluorescence biosensors for the detection of HAase. Furthermore, this new biosensor has already been applied in the study of urine samples, and the detection results were consistent with those obtained by the clinical tests.	bladder
Nomograms to predict individual prognosis of patients with squamous cell carcinoma of the urinary bladder.	BACKGROUND: On the basis of some significant clinical parameters, we had an intent to establish nomograms for estimating the prognosis of patients with squamous cell carcinoma of the urinary bladder (SCCB), including overall survival (OS) and cancer-specific survival (CSS). METHODS: The data of 1210 patients diagnosed with SCCB between 2004 and 2014,were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The Cox proportional hazards regression model was applied to evaluate the association between variables and survival. Nomograms were constructed to predict the OS and CSS of an individual patient based on the Cox model. In the end, the performance of nomograms was internally validated by using calibration curves, concordance index (C-index), and k-fold cross-validation. RESULTS: Several common indicators were taken into the two nomograms (OS and CSS), including age at diagnosis, marital status, sex, TNM stage, surgical approach, tumor size, and lymph node ratio while the OS nomogram additionally contained race, grade, and chemotherapy. They had an excellent predictive accuracy on 1- and 3- year OS and CSS with C-index of 0.733 (95% confidence interval [CI], 0.717-0.749) for OS and 0.724 (95% CI, 0.707-0.741) for CSS. All calibration curves showed great consistency between actual survival and predictive survival. CONCLUSIONS: The nomograms with improved accuracy and applicability on predicting the survival outcome of patients with SCCB would provide a reliable tool to help clinicians to evaluate the risk of patients and make individual treatment strategies.	bladder
Functionalized Upconversion Nanoparticles for Targeted Labelling of Bladder Cancer Cells.	Bladder cancer is the ninth most common cancer worldwide. Due to a high risk of recurrence and progression of bladder cancer, every patient needs long-term surveillance, which includes regular cystoscopy, sometimes followed by a biopsy of suspicious lesions or resections of recurring tumours. This study addresses the development of novel biohybrid nanocomplexes representing upconversion nanoparticles (UCNP) coupled to antibodies for photoluminescent (PL) detection of bladder cancer cells. Carrying specific antibodies, these nanoconjugates selectively bind to urothelial carcinoma cells and make them visible by emitting visible PL upon excitation with deeply penetrating near-infrared light. UCNP were coated with a silica layer and linked to anti-Glypican-1 antibody MIL38 via silica-specific solid-binding peptide. Conjugates have been shown to specifically attach to urothelial carcinoma cells with high expression of Glypican-1. This result highlights the potential of produced conjugates and conjugation technology for further studies of their application in the tumour detection and fluorescence-guided resection.	bladder
Adipose-Derived Stem Cells Inhibited the Proliferation of Bladder Tumor Cells by S Phase Arrest and Wnt/β-Catenin Pathway.	Adipose-derived stem cells (ADSCs), which are present in most organs and tissues, were evaluated as a novel medium for stem cell therapy. In this study, we investigated the effects and underlying mechanisms of ADSCs in bladder tumor (BT) cells. SV-HUC, T24, and EJ cells were cultured with ADSCs and conditioned medium from ADSCs (ADSC-CM). We observed that in routine culture, ADSCs significantly inhibited the proliferation of T24 and EJ cells in a dose-dependent manner. In addition, ADSC-CM attenuated the viability of T24 and EJ cells in a dose-dependent manner. Cell cycle analysis indicated that ADSC-CM was capable of inducing T24 and EJ cells S phase arrest and downregulating the expression of CDK 1, whereas the expression of cyclin A was increased. ADSC-CM could induce apoptosis in T24 cells. The mechanism of this effect likely involved the caspase3/7 pathway and Wnt/β-catenin pathway. These findings demonstrated that ADSCs could inhibit the proliferation of BT cells via secretory factors.	bladder
Metastatic non-muscle invasive bladder can-cer with cervical lymph node metastasis.	Bladder cancer is a common cancer that may present as superficial, invasive, or metastatic disease. Non-muscle-invasive bladder cancer (NMIBC) represents the majority of bladder cancer diagnoses, but represents a spectrum of disease with a variable clinical course, notably for significant risk of recurrence and potential for progression. NMIBC metastasis to distant organs without local invasion or regional metastasis is a very rare occurrence, so there are limi-ted case reports about early metastasis in the literature.	bladder
GABPA is a master regulator of luminal identity and restrains aggressive diseases in bladder cancer.	TERT promoter mutations occur in the majority of glioblastoma, bladder cancer (BC), and other malignancies while the ETS family transcription factors GABPA and its partner GABPB1 activate the mutant TERT promoter and telomerase in these tumors. GABPA depletion or the disruption of the GABPA/GABPB1 complex by knocking down GABPB1 was shown to inhibit telomerase, thereby eliminating the tumorigenic potential of glioblastoma cells. GABPA/B1 is thus suggested as a cancer therapeutic target. However, it is unclear about its role in BC. Here we unexpectedly observed that GABPA ablation inhibited TERT expression, but robustly increased proliferation, stem, and invasive phenotypes and cisplatin resistance in BC cells, while its overexpression exhibited opposite effects, and inhibited in vivo metastasizing in a xenograft transplant model. Mechanistically, GABPA directly activates the transcription of FoxA1 and GATA3, key transcription factors driving luminal differentiation of urothelial cells. Consistently, TCGA/GEO dataset analyses show that GABPA expression is correlated positively with luminal while negatively with basal signatures. Luminal tumors express higher GABPA than do basal ones. Lower GABPA expression is associated with the GABPA gene methylation or deletion (especially in basal subtype of BC tumors), and predicted significantly shorter patient survival based on TCGA and our cohort of BC patient analyses. Taken together, GABPA dictates luminal identity of BC cells and inhibits aggressive diseases in BC by promoting cellular differentiation despite its stimulatory effect on telomerase/TERT activation. Given these biological functions and its frequent methylation and/or deletion, GABPA serves as a tumor suppressor rather than oncogenic factor in BC. The GABPA effect on oncogenesis is context-dependent and its targeting for telomerase inhibition in BC may promote disease metastasizing.	bladder
Importance of PNO1 for growth and survival of urinary bladder carcinoma: Role in core-regulatory circuitry.	PNO1 (partner of Nob1) was known as a RNA-binding protein in humans, and its ortholog PNO1 was reported to participate ribosome and proteasome biogenesis in yeasts. Yet there have been few studies about its functions in mammalian cells, and so far its role in human cells has never been reported, especially in urinary bladder cancer (UBC).We interrogated the cellular functions and clinical significance of PNO1 in, and its molecular mechanism through microarrays and bioinformatics analysis. Our findings support that PNO1 participates in promoting proliferation and colonogenesis, while reducing apoptosis of UBC cells, and is also predicted to be associated with the migration and metastasis of UBC PNO1 knockdown (KD) attenuated the tumorigenesis ability of UBC in mouse. PNO1 KD led to the altered expression of 1543 genes that are involved in a number of signalling pathways, biological functions and regulation networks. CD44, PTGS2, cyclin D1, CDK1, IL-8, FRA1, as well as mTOR, p70 S6 kinase, p38 and Caspase-3 proteins were all down-regulated in PNO1 KD cells, suggesting the involvement of PNO1 in inflammatory responses, cell cycle regulation, chemotaxis, cell growth and proliferation, apoptosis, cell migration and invasiveness. This study will enhance our understanding of the molecular mechanism of UBC and may eventually provide novel targets for individualized cancer therapy.	bladder
LncRNA CASC15 functions as an oncogene by sponging miR-130b-3p in bladder cancer.	OBJECTIVE: Recent studies have revealed that long noncoding RNAs (lncRNAs) are dysregulated in malignant tumors and participates in carcinogenesis. The purpose of our study was to uncover the mechanisms underlying lncRNA CASC15 in bladder cancer (BLCA). PATIENTS AND METHODS: In this research, Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was performed to detect cancer susceptibility candidate 15 (CASC15) expression in BLCA samples and cells. Besides, the wound healing assay and transwell assay were performed in BLCA cells after CASC15 was knocked down. Furthermore, the bioinformatics analysis and dual-luciferase reporter assay were conducted to explore the target miRNA of CASC15, which was further verified through rescue experiments in BLCA cells. RESULTS: CASC15 expression was upregulated in BLCA tissue samples. Moreover, CASC15 downregulated the miR-130b-3p expression and promoted cell migration and invasion in BLCA in vitro. The rescue experiments also revealed that the inhibitory effects by the silence of CASC15 could be reversed through the inhibition of miR-130b-3p. CONCLUSIONS: Our study suggested a vital regulatory mechanism of CASC15 in BLCA, and the CASC15/miR-130b-3p axis might serve as a new therapeutic interventional target for BLCA patients.	bladder
Prognosis of early stage small cell bladder cancer is not always dismal.	BACKGROUND: Small cell carcinoma of the urinary bladder (SCCB) is an extremely rare malignancy which is often associated with poor survival outcome. Literature reporting such disease is scarce. There is no standardised management. This retrospective audit examines a UK Cancer Centre's SCCB management and survival outcomes. METHODS: Histopathology database at Nottingham University Hospitals, UK, was used to identify patients diagnosed with SCCB from January 2008 to January 2016. RESULTS: 27 patients had confirmed diagnosis of SCCB. Mean age at diagnosis was 68.7 (range 37-90). 30% of the cases had pure small cell histology, while the rest were mixed histological subtype. Of the 12 patients with early stage disease (stage I and II), three had radical cystectomy and chemotherapy, six had both radiotherapy and chemotherapy, two had either radiotherapy or chemotherapy alone, and one declined active treatment. Of the 12 patients with advanced disease (stage III and IV), four had chemotherapy alone, four had both radiotherapy and chemotherapy and four was for best supportive care. 13 out of 16 patients who had chemotherapy received combination of carboplatin and etoposide. Patients with advanced stage disease had medial survival of 9 months (95% CI 3.9 to 14.1 months). The median survival for patients with early disease was not reached. There is significant difference in survival between early and late stage disease (p value 0.008, Log rank test). CONCLUSIONS: Our results demonstrated a reasonable survival outcome in early stage SCCB patients. Radical multimodality treatment options should not be precluded in patients with early stage SCCB.	bladder
Neurofibromatosis-1 and Rhabdomyosarcoma: An Unusual Recurrence.	Neurofibromatosis-1 has a known increased risk of malignancy with rhabdomyosarcoma occurring in up to 6% of patients. Here we report on an 8-year-old male with a history of Neurofibromatosis-1 and previously treated stage 3, group III bladder/prostate embryonal rhabdomyosarcoma (diagnosed at 18 months old) who presented with penile swelling concerning for priapism. Imaging and subsequent biopsy confirmed embryonal rhabdomyosarcoma of the penile corporal bodies. Penile rhabdomyosarcoma is exceedingly rare, with less than 15 case reports in the literature. Our patient received chemoradiation per D9803 with organ preserving local control and is doing well 3 months after treatment.	bladder
Cabozantinib in Combination with Immunotherapy for Advanced Renal Cell Carcinoma and Urothelial Carcinoma: Rationale and Clinical Evidence.	The treatment landscape for metastatic renal cell carcinoma (mRCC) and urothelial carcinoma (mUC) has evolved rapidly in recent years with the approval of several checkpoint inhibitors. Despite these advances, survival rates for metastatic disease remain poor, and additional strategies will be needed to improve the efficacy of checkpoint inhibitors. Combining anti-VEGF/VEGFR agents with checkpoint inhibitors has emerged as a potential strategy to advance the immunotherapy paradigm, because VEGF inhibitors have immunomodulatory potential. Cabozantinib is a tyrosine kinase inhibitor (TKI) whose targets include MET, AXL, and VEGFR2. Cabozantinib has a unique immunomodulatory profile and has demonstrated clinical efficacy as a monotherapy in mRCC and mUC, making it a potentially suitable partner for checkpoint inhibitor therapy. In this review, we summarize the current status of immunotherapy for mRCC and mUC and discuss the development of immunotherapy-TKI combinations, with a focus on cabozantinib. We discuss the rationale for such combinations based on our growing understanding of the tumor microenvironment, and we review in detail the preclinical and clinical studies supporting their use.	bladder
Preoperative Plasma Fibrinogen and D-dimer as Prognostic Biomarkers for Non-Muscle-Invasive Bladder Cancer.	PURPOSE: To assess the ability of preoperative plasma fibrinogen and D-dimer as biomarkers to predict survival outcomes in patients with non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: A total of 206 NMIBC patients receiving transurethral resection of bladder tumor (TURBT) were assessed in our retrospective study. The cutoff values of fibrinogen and D-dimer were determined using receiver operating characteristic curve analysis. Cox regression analyses were adopted to assess the influence of these two parameters on recurrence-free survival (RFS) and progression-free survival (PFS). RESULTS: The cutoff values of fibrinogen and D-dimer were 3.56 g/L and 0.48 μg/mL, respectively. Kaplan-Meier analysis demonstrated that high fibrinogen and D-dimer levels were significantly related to poor RFS (all P < .001) and PFS (all P < .001). Moreover, patients with elevated fibrinogen levels tended to have high tumor grade (P = .033), advanced pathologic T stage (P < .001), and multiple tumor lesions (P = .019). Significant associations of high D-dimer levels with advanced pathologic T stage (P = .026), large tumor size (P = .012), and multiple tumor lesions (P = .006) were found. In addition, multivariate analysis revealed that plasma fibrinogen and D-dimer were all independent predictive factors for RFS (P = .029 and .001, respectively) and PFS (P = .023 and .003, respectively). CONCLUSION: High levels of preoperative plasma fibrinogen and D-dimer may indicate advanced clinicopathologic features and worse prognosis, suggesting that these two coagulation parameters could be used as prognostic biomarkers for NMIBC patients.	bladder
Sex Differences in Urothelial Bladder Cancer Survival.	BACKGROUND: While urinary bladder cancer is consistently more common in men worldwide, women have poorer prognosis. The aim of this study was to outline sex differences in prognostic factors and clinical management and to explore whether these can explain the poorer urinary bladder cancer outcome in women. PATIENTS AND METHODS: We performed a population-based cohort study including all patients diagnosed with urothelial bladder cancer between 1997 and 2014 at age 18 to 89 who had data recorded in the Swedish Urinary Bladder Cancer Register (n = 36,344). Female-to-male odds ratios for clinical management parameters were estimated by logistic regression. To quantify sex differences in bladder cancer-specific survival, we estimated empirical survival proportions and mortality rates as well as applied flexible parametric models to estimate female-to-male hazard ratios and survival proportions over follow-up. Adjusted models included age, year, World Health Organization grade, stage, marital status, education, health care region, birth country, and comorbidity. RESULTS: Except for an adverse stage distribution in women, we found no evidence of unequal clinical management. Among those diagnosed with bladder cancer, women had a higher bladder cancer mortality (adjusted hazard ratio, 1.15; 95% confidence interval, 1.08-1.23) driven by muscle-invasive tumors (adjusted hazard ratio, 1.24; 95% confidence interval, 1.14-1.34). The female survival disadvantage was confined to the first 2 years after diagnosis. CONCLUSION: The excess bladder cancer mortality in women is limited to those diagnosed with muscle-invasive tumors and cannot be explained by the examined clinicopathologic factors. Further investigations of sex differences in therapeutic procedures and outcomes, including complications, of muscle-invasive bladder cancer, must be performed.	bladder
NNT-AS1 enhances bladder cancer cell growth by targeting miR-1301-3p/PODXL axis and activating Wnt pathway.	As a tumor involved in the urinary system, bladder cancer (BC) seriously threatens human health. Emerging as crucial biomarkers, long noncoding RNAs (lncRNAs) play an important role in the regulation of many cancers. lncRNA NNT-AS1 has been studied in a series of cancers, whereas its role and potential molecular mechanism was poorly understood in BC. Here, we found that NNT-AS1 was upregulated in BC cells. Functionally, the silencing of NNT-AS1 inhibited cell proliferation, migration, invasion, and endothelial-mesenchymal transition. Furthermore, the apoptosis of BC cells was induced upon NNT-AS1 knockdown. Later, miR-1301-3p, the downstream gene of NNT-AS1, was found at a low level in BC cells. In addition, we found that miR-1301-3p targeted to PODXL. PODXL expression downregulated in NNT-AS1-silenced cells was restored by miR-1301-3p inhibition. Importantly, NNT-AS1 was discovered to activate Wnt pathway, and the treatment of LiCl recovered the repressive role of NNT-AS1 silencing in BC cell growth. Through restoration assays, we observed that PODXL overexpressing countervailed NNT-AS1 depletion-mediated suppression on BC cell growth and Wnt pathway. These data suggested that NNT-AS1 enhances BC cell growth and activates Wnt pathway by targeting miR-1301-3p/PODXL axis.	bladder
Current Clinical Trials in Non-muscle-Invasive Bladder Cancer: Heightened Need in an Era of Chronic BCG Shortage.	PURPOSE OF REVIEW: BCG is the gold standard agent used in high-risk non-muscle-invasive bladder cancer (NMIBC) that is amenable to bladder sparing management. However, recent BCG shortages appear to be a chronic problem. There are limited effective intravesical options in lieu of BCG or in patients in whom BCG is not effective. This review aims to highlight emerging bladder sparing therapies and trials for NMIBC. RECENT FINDINGS: Patients with high-risk NMIBC who do not respond to BCG are at increased risk for progression and death from bladder cancer. There are a variety of clinical trials exploring different therapeutic approaches including checkpoint inhibition, novel chemotherapy and drug delivery, viral and gene therapy, vaccines, and targeted therapy. In the era of limited supply of BCG, there is a need for both effective first-line alternatives as and options for patients who do not respond to BCG. Fortunately, there are a variety of active trials and mechanisms exploring these areas aggressively.	bladder